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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1460-1471. Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-07-030726. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2006-07-030726v1 109/4/1460    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ghinassi, B. Articles by Migliaccio, A. R. Search for Related Content PubMed PubMed Citation Articles by Ghinassi, B. Articles by Migliaccio, A. R. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor Barbara Ghinassi1,2, Massimo Sanchez3, Fabrizio Martelli1, Giovanni Amabile3, Alessandro Maria Vannucchi4, Giovanni Migliaccio3, Stuart H. Orkin5, and Anna Rita Migliaccio1,6 1 Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy; 2 Department of Biomorphology, University G. D'Annunzio, Chieti, Italy; 3 Department of Cell Biology and Neurosciences, Istituto Superiore Sanità, Rome, Italy; 4 Department of Hematology and Oncology, University of Florence, Italy; 5 Department of Pediatric Oncology, Children's Hospital, Dana Farber Cancer Institute, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA; 6 Department of Medicine and Myeloproliferative Disease–Research Consortium (Pathology), University of Illinois at Chicago Recent evidence suggests that mutations in the Gata1 gene may alter the proliferation/differentiation potential of hemopoietic progenitors. By single-cell cloning and sequential replating experiments of prospectively isolated progenitor cells, we demonstrate here that the hypomorphic Gata1low mutation increases the proliferation potential of a unique class of progenitor cells, similar in phenotype to adult common erythroid/megakaryocytic progenitors (MEPs), but with the "unique" capacity to generate erythroblasts, megakaryocytes, and mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast cell progenitors (MCPs) are not detectable in the marrow from these mutants. At the single-cell level, about 11% of Gata1low progenitor cells, including MEPs, generate cells that will continue to proliferate in cultures for up to 4 months. In agreement with these results, trilineage (erythroid, megakaryocytic, and mastocytic) cell lines are consistently isolated from bone marrow and spleen cells of Gata1low mice. These results confirm the crucial role played by Gata1 in hematopoietic commitment and identify, as a new target for the Gata1 action, the restriction point at which common myeloid progenitors become either MEPs or MCPs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: On the origins of megakaryocytes John D. Crispino Blood 2007 109: 1340-1341. [Full Text] [PDF] This article has been cited by other articles: S. G. Olthof, S. Fatrai, A. L. Drayer, M. R. Tyl, E. Vellenga, and J. J. Schuringa Downregulation of Signal Transducer and Activator of Transcription 5 (STAT5) in CD34+ Cells Promotes Megakaryocytic Development, Whereas Activation of STAT5 Drives Erythropoiesis Stem Cells, July 1, 2008; 26(7): 1732 - 1742. [Abstract] [Full Text] [PDF] F. Martelli, B. Ghinassi, R. Lorenzini, A. M. Vannucchi, R. A. Rana, M. Nishikawa, S. Partamian, G. Migliaccio, and A. R. Migliaccio Thrombopoietin Inhibits Murine Mast Cell Differentiation Stem Cells, April 1, 2008; 26(4): 912 - 919. [Abstract] [Full Text] [PDF] A. B. Cantor, H. Iwasaki, Y. Arinobu, T. B. Moran, H. Shigematsu, M. R. Sullivan, K. Akashi, and S. H. Orkin Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage J. Exp. Med., March 17, 2008; 205(3): 611 - 624. [Abstract] [Full Text] [PDF] D. Metcalf, I. Majewski, S. Mifsud, L. Di Rago, and W. S. Alexander Clonogenic mast cell progenitors and their excess numbers in chimeric BALB/c mice with inactivated GATA-1 PNAS, November 20, 2007; 104(47): 18642 - 18647. [Abstract] [Full Text] [PDF] J. M. Salmon, N. J. Slater, M. A. Hall, M. P. McCormack, S. L. Nutt, S. M. Jane, and D. J. Curtis Aberrant mast-cell differentiation in mice lacking the stem-cell leukemia gene Blood, November 15, 2007; 110(10): 3573 - 3581. [Abstract] [Full Text] [PDF] M. Kobayashi and M. Yamamoto Regulation of GATA1 Gene Expression J. Biochem., July 1, 2007; 142(1): 1 - 10. [Abstract] [Full Text] [PDF] C. Slape, H. Hartung, Y.-W. Lin, J. Bies, L. Wolff, and P. D. Aplan Retroviral Insertional Mutagenesis Identifies Genes that Collaborate with NUP98-HOXD13 during Leukemic Transformation Cancer Res., June 1, 2007; 67(11): 5148 - 5155. [Abstract] [Full Text] [PDF]

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